The present application claims priority from Korean Patent Application No. 10-2016-0083361, filed on Jul. 1, 2016, the entire content of which is incorporated herein by reference.
Follicular thyroid carcinoma (FTC), which accounts for about 20% of all thyroid cancers, is frequently found in women and belongs to a differentiated thyroid cancer with good prognosis. Thyroid follicular carcinoma is mainly found in older ages, compared to papillary thyroid carcinoma which is the most common thyroid cancer. Papillary thyroid carcinoma is mainly metastasized through the lymph nodes, whereas thyroid follicular carcinoma through the blood vessels. On the other hand, papillary thyroid carcinoma can be diagnosed relatively easily through fine needle aspiration test by observing characteristic nuclear morphology. However, thyroid follicular carcinoma has difficulties in accurately diagnosing it because definite criteria have not been established. In particular, thyroid follicular carcinoma can be mistaken for follicular adenoma because 20-30% of follicular adenomas, which are benign tumors of the thyroid gland, cannot be distinguished from thyroid follicular carcinoma by fine needle aspiration test.
Currently, the confirmation of thyroid follicular carcinoma is possible only be collecting thyroid tissues through surgery and identifying the pathology in the tissues. In this way, pathologic examination including surgery is first performed by the surgical excision of the half of the thyroid where nodules is found, followed by histological examination. In case where thyroid follicular carcinoma is diagnosed, such a method is a very cumbersome method because the other half of the thyroid must be removed again through surgery, except for early cancer with good prognosis. Therefore, it is necessary to develop a biomarker that can distinguish thyroid follicular carcinoma from follicular adenoma and confirm thyroid follicular carcinoma, in the thyroid tissue or blood obtained during the fine needle aspiration test. In particular, when a protein-based biomarker is developed, the level of expression of the marker can be measured using an antibody or the like, so that information necessary for diagnosis can be quickly obtained, without a necessity to perform surgery for pathologic examination.
Mutations in genes such as BRAF, RET/PTC, RAS, PAX8/PPAR gamma, and P53, which have been proposed as biomarkers for thyroid follicular cancer, are not actually used in diagnosis because their incidence is not high. In addition, studies in which the expression levels of five genes such as ELMO1, EMCN, ITIH5, KCNAB1, and SLCO2A1 were reduced in thyroid follicular carcinoma tissues compared to follicular adenoma tissues, suggested a possibility of developing such genes as a marker that can distinguish follicular adenoma from thyroid follicular carcinoma. However, there is a limitation to utilize such genes as a marker; including the necessity of the process of extracting mRNAs from tissue (Pfeifer et al. BMC Medical Genomics 2013, 6:380). Protein markers that identify thyroid cancer are used as immunohistochemistry (Wiseman S M et al., Annals of Surgical Oncology 2008, 15:2811-2826), but their specificity is too low to distinguish thyroid follicular carcinoma from follicular adenoma.
Therefore, it is urgent to develop a biomarker that can specifically distinguish thyroid follicular carcinoma from benign tumors such as follicular adenoma.